Background: Duchenne musclar dystrophy (DMD) is an X-linked recessive disease caused by mutations of dystrophin gene, there is no effective treatment for this disorder at present. Plasmidmediated
gene therapy is a promising therapeutical approach for the treatment of DMD. One of
the major issues with plasmid-mediated gene therapy for DMD is poor transfection efficiency and distribution. The herpes simplex virus protein VP22 has the capacity to spread from a primary
transduced cell to surrounding cells and improve the outcome of gene transfer. To improve the efficiency of plasmid-mediated gene therapy and investigate the utility of the intercellular trafficking
properties of VP22-linked protein for the treatment for DMD, expression vectors for C-terminal versions of VP22-microdystrophin fusion protein was constructed and the VP22-mediated shuttle effect was evaluated both in vitro and in vivo.
Results: Our results clearly demonstrate that the VP22-microdystrophin fusion protein could transport into C2C12 cells from 3T3 cells, moreover, the VP22-microdystrophin fusion protein
enhanced greatly the amount of microdystrophin that accumulated following microdystrophin gene
transfer in both transfected 3T3 cells and in the muscles of dystrophin-deficient (mdx) mice.
Conclusion: These results highlight the efficiency of the VP22-mediated intercellular protein delivery for potential therapy of DMD and suggested that protein transduction may be a potential
and versatile tool to enhance the effects of gene delivery for somatic gene therapy of DMD.National Natural Science Foundation of China (30370510, 30170337); CMB Fund (4209347); the Key Project of the State Ministry of Public Health (2001321); and National Nature Science Foundation of China (30400322)